DESCRIPTION: The project proposes to test the hypothesis that abnormal maternal and/or fetal folate receptor increases environmentally-induced neural tube defects (NTD), and that the lack of folate results in abnormal gene expression during critical developmental periods. Arsenate will be used as a model teratogen to induce NTD. For aim 1, knockout mice have been developed for folate binding protein 1 (FBP-1) and folate binding protein 2 (FBP-2). Animals possessing different FBP status will be examined for NTD and the effect of arsenate will be examined. In aim 2, fusion protein transgenics animals will be studied. These animals will have FBP-1 and FBP-2 fusions with green fluorescence proteins (different GFPs that give emission spectra) in order to specifically detect the expression of each FBP so that the patterns of expression of each can be determined. In aim 3, the effect of teratogenic concentrations of arsenate on expression of a number of transcription factor and growth factor genes will be examined. As well, the expression of cell cycle control and DNA repair genes will be examined. In aim 4, the effect on neural tube closure of supplemental folate treatment on FBP compromised animals will be examined, as will the effect of arsenate.